Active clinical trials for "Tuberous Sclerosis"

Eighty percent of patients with tuberous sclerosis complex (TSC) have renal angiomyolipomata. These lesions grow and can lead to significant morbidity by hemorrhage or renal failure. Understanding the natural history of these lesions and understanding which lesions may be more prone to grow quickly or develop aneurysms that predispose to hemorrhage will greatly assist clinical care of patients with TSC. The objective is to test the hypothesis that serial MR and CT imaging will allow objective, reproducible quantification of angiomyolipoma growth by volumetric analysis, and analysis of lesions characteristics will identify angiomyolipomata with rapid growth potential that would require intervention. The specific aim of this proposal is to collect clinically obtained serial abdominal imaging from the Tuberous Sclerosis Natural History Consortium Centers and analyze the volume and adiposity of the individual angiomyolipomata. The growth rate is hypothesized to have an inverse relationship to adiposity. Yearly renal MR or CT imaging will be performed of patients with TSC. The images will be coded at the site of acquisition, and transferred via VPN to a secure server at Cincinnati Children's Hospital Medical Center. Using innovative imaging processing software (Cincinnati Children's Hospital Image Processing Software (CCHIPS), the image data will be segmented to reveal various tissue components based on signal intensities. Different signal intensities can differentiate normal renal parenchyma, and renal angiomyolipomata. Using the imaging data and the novel software, the volume of an individual angiomyolipoma, as well as the adiposity will be determined. Imaging at enrollment (year 1) will serve as baseline. At years two and three, the lesions will undergo repeat analysis. Angiomyolipoma growth rates and adiposity over three years will be analyzed to test the hypothesis above.

The proposed research project is aimed at further characterization of sleep problems and evaluation of their impact in children and adults with TSC, excluding epilepsy as contributing factor. Questionnaire-based studies have shown that sleep problems occur in up to half of the children and a third of adults with tuberous sclerosis complex (TSC). However, there is only limited information on the nature of sleep problems and their impact on patients with TSC and their families.

Both Neurofibromatosis type 1 (NF1) and Tuberous Sclerosis Complex (TSC) are highly heterogeneous diseases. Cognitive features seem to vary widely even between family members carrying the same mutation. This phenotypic variability is not well understood, but is generally assumed to be caused by modifier genes which regulate the affected pathways. However, recent studies brought forward an alternative explanation for the phenotypic variability. Post-mortem studies showed that second hit mutations causing loss of the second ('healthy') allele are more widespread than previously believed. These loss of heterozygosity (LOH) mutations cause bi-allelic loss of the disease-linked gene and are known to cause the gross of somatic features in both diseases (like neurofibromas and hamartomas). Hence, it could be the stochastic occurrence of second-hit mutations in the brain are the cause of the variable cognitive phenotypes. To investigate to what extent these LOH mutations in the brain contribute to the phenotype and to what extent this variation is due to genetic modifiers factors is unknown. The investigators therefore propose to elucidate this variability by comparing the correlation of cognitive features of monozygotic twins with NF1 or TSC to healthy twins in the population. If modifier genes are the cause of the variability of cognitive features in NF1 and TSC the investigators expect that the variability in cognitive tests in monozygotic twins is the same as monozygotic twins in the healthy population. However, if the variability is caused by the occurrence of LOH mutations, the investigators expect to have a lower correlation in our monozygotic patients compared to the healthy twins.

This study aims to investigate the factors (clinical, care-related and genetic) affecting renal outcome in patients with TSC (Tuberous sclerosis complex)

Tuberous Sclerosis is a rare genetic disorder that affects about one in 15,000 individuals. It is part of the phacomatoses: a germline mutation of the gene Tuberous Sclerosis Complex 1 (TSC1) or TSC2 causes a protein dysfunction, hamartin and tuberin respectively, leading to mTOR signaling pathway activation, thus tumors rise on the skin but also brain, eyes, kidneys, heart. Thanks to the advent of sequencing techniques of the human genome, genes involved were found twenty years ago. Most commonly, these are de novo private mutations and autosomal dominant Mendelian transmission. About 15% of patients have a phenotype corresponding to the disease but no mutation is found. Although the initial clinical description was in 1880, publications regularly describe new signs in Tuberous Sclerosis, especially for skin. Cutaneous manifestations are important in the diagnostic criteria of the disease and often even the first sign of appeal. However, no data is available on the relationship between genotype and dermatological phenotype. Therefore the investigator intend to review all cutaneous finding in Tuberous Sclerosis patient and try to link with their mutation.